Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis

Ann Hematol. 2019 Oct;98(10):2319-2328. doi: 10.1007/s00277-019-03766-z. Epub 2019 Aug 8.

Abstract

Triple-negative primary myelofibrosis (TN-PMF) and other myeloid neoplasms with associated bone marrow fibrosis such as the myelodysplastic syndromes (MDS-F) or the myelodysplastic/myeloproliferative neoplasms (MDS/MPN-F) are rare entities, often difficult to distinguish from each other. Thirty-four patients previously diagnosed with TN-PMF (n = 14), MDS-F (n = 18), or MDS/MPN-F (n = 2) were included in the present study. After central revision of the bone marrow histology, diagnoses according to the 2016-WHO classification were TN-PMF (n = 6), MDS-F (n = 19), and MDS/MPN-F (n = 9), with TN-PMF genotype representing only 4% of a cohort of 141 molecularly annotated PMF. Genomic classification according to next-generation sequencing and cytogenetic study was performed in 28 cases. Median number of mutations was 4 (range 1-7) in cases with TP53 disruption/aneuploidy or with chromatin-spliceosome mutations versus 1 mutation (range 0-2) in other molecular subgroups (p < 0.0001). The number of mutations and the molecular classification were better than PMF and MDS conventional scoring systems to predict survival and progression to acute leukemia. In conclusion, TN-PMF is an uncommon entity when the 2016 WHO criteria are strictly applied. Genomic classification may help in the prognostic assessment of patients with myeloid neoplasms with bone marrow fibrosis.

Keywords: Diagnosis; Genomic classification; Myelodysplastic syndromes; Primary myelofibrosis; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms* / classification
  • Hematologic Neoplasms* / genetics
  • Hematologic Neoplasms* / mortality
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Leukemia, Myeloid, Acute* / classification
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes* / classification
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / mortality
  • Primary Myelofibrosis* / classification
  • Primary Myelofibrosis* / genetics
  • Primary Myelofibrosis* / mortality
  • Survival Rate